T-cell-mediated lympholysis was generated in vitro against trinitrophenyl-(TNP-) modified syngeneic murine spleen cells (TNP-self). Results obtained during this report period indicate that radioresistant, theta-negative, spleenic adherent cells (SAC) are required for the generation of cytotoxic effector cells to TNP-self (and alloantigens), although the SAC do not determine H-2 restriction. The SAC required in the cytotoxic responses express Ia antigens which map to the I-A and I-E/C surbregions. The control of cytotoxic responses to TNP associated with D region self products requires a cytotoxic response to K super k modified self determinants. Cytotoxic responses could be generated against cells modified with low concentrations of TNBS for the H-2 k,a but not the H-2 b,d haplotypes. These strain-dependent differences could be detected at the stimulating and target cell levels, and possibly at the responding cell levels, since the H-2K,a but not the H-2b,d strains could be easily primed in vivo for enhanced secondary in vitro cytotoxic responses to TNP-self. In vivo priming to TNP-self resulted in enhanced secondary responses for cytotoxicity but in suppressed delayed hypersensitivity reactions.